PuSH - Publikationsserver des Helmholtz Zentrums München

Koprulu, M.* ; Smith-Byrne, K.* ; Ferolito, B.R.* ; Macdonald-Dunlop, E.* ; Luan, J.* ; Hedman, K.* ; Ogamba, C.F.* ; Kuliesius, J.* ; Repetto, L.* ; Ramisch, A.* ; Abbasi, F.* ; Johan Ärnlöv,* ; Assimes, T.L.* ; Björck, H.M.* ; Björkander, S.* ; Bøttcher, M.* ; Butterworth, A.S.* ; Chen, Z.M.* ; Cho, K.* ; Clarke, R.J.* ; Cox, S.R.* ; Czene, K.* ; Danesh, J.* ; Dedoussis, G.* ; Elmståhl, S.* ; Eriksson, N.* ; Eriksson, P.* ; Esko, T.* ; Ferreiro-Iglesias, A.* ; Franks, P.W.* ; Fu, J.* ; Gaziano, J.M.* ; Ghanbari, M.* ; Gieger, C. ; Gilly, A. ; Grallert, H. ; Gunter, M.J.* ; Gustafsson, S.* ; Göteson, A.* ; Hall, P.* ; Hansson, O.* ; Harris, S.E.* ; Hayward, C.* ; Herder, C.* ; Hernandez-Pacheco, N.* ; Hijazi, Z.* ; Hillary, R.F.* ; Hopewell, J.C.* ; Hu, S.* ; Hwang, S.* ; Jern, C.* ; Johansson, ?.* ; Jonsson, L.* ; Kalnapenkis, A.* ; Kerrison, N.D.* ; Kho, P.F.* ; Klarić, L.* ; Kohleick, L.* ; Kraft, J.* ; Landén, M.* ; Levy, D.* ; Li, L.* ; Lind, L.* ; Long, J.* ; Mattsson, N.* ; Melén, E.* ; Merid, S.K.* ; Mertins, P.* ; Michaëlsson, K.* ; Möller, P.* ; Murgia, F.* ; Nyegaard, M.* ; Park, Y.-C. ; Pearson, E.R.* ; Peters, J.* ; Petrie, J.* ; Png, G. ; Polašek, O.* ; Prins, B.P.* ; Ripke, S.* ; Roden, M.* ; Rohde, P.D.* ; Said, S.* ; Shen, X.* ; Schwenk, J.M.* ; Siegbahn, A.* ; Smith, J.G.* ; Stanne, T.M.* ; Suhre, K.* ; Sundström, J.* ; Thorand, B. ; Valdés‐Márquez, E.* ; Vallerga, C.L.* ; Meurs, J.B.J.v.* ; Viñuela, A.* ; Võsa, U.* ; Wallentin, L.* ; Walters, R.G.* ; Wareham, N.J.* ; Weber, J.E.*

Multi-cohort proteogenomic analyses reveal genetic effects across the proteome and diseasome.

Cell 189, 3339-3357.e11 (2026)
Verlagsversion Forschungsdaten DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Understanding the genetic regulation of circulating protein levels can provide new insights into disease mechanisms. Here, we present the largest proteogenomic study to date (n = 78,664 participants across 38 studies), identifying >24,000 protein quantitative trait loci (QTLs) associated with 1,116 proteins, acting near to (n = 5,040) or distant (n = 19,698) from the cognate gene. Using machine learning-guided effector gene assignment, we provide genetic evidence for pathways, cell types, and tissues that modulate circulating protein levels, highlighting N-linked glycosylation as an important regulatory pathway. We demonstrate that genetic instruments of protein production/function ("cis") versus modulation ("trans") reveal distinct phenotypic insights. We identify proteins as candidates for drug targets and engagement (e.g., plasma furin and cardiovascular diseases) by comparing cis-based genetic evidence with protein-disease associations. Systematic triangulation of trans-protein QTLs (pQTLs) with genetic and protein associations across many diseases highlights potential drug repurposing opportunities, e.g., tyrosine kinase 2 (TYK2) inhibitors for rheumatoid arthritis. Our multi-cohort meta-analyses generate proteogenomic insights into disease mechanisms and new treatment opportunities.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Proteome ; Proteogenomics ; Gene ; Effector ; Phenotype ; Proteomics ; Genetic Screen ; Drug Repositioning; Associations; Metaanalysis; Variants; Pathways; Insights; Health
ISSN (print) / ISBN 0092-8674
e-ISSN 1097-4172
Zeitschrift Cell
Quellenangaben Band: 189, Heft: 11, Seiten: 3339-3357.e11 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Cambridge, Mass.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
Institute of Translational Genomics (ITG)
Förderungen Gates Cambridge Trust
Sir Henry Dale Fellowship - Royal Society
Estonian Research Council
European Commission
Swedish Research Council
Novo Nordisk Foundation
Vinnova
Swedish Foundation for Strategic Research (LUDC-IRC)
Exodiab
European Research Council (ERC)
Dutch Research Council (NWO) VICI
Dutch Research Council (NWO) KIC
Stichting Ammodo
Dutch Heart Foundation
Department of Veterans Affairs
Sir Henry Dale Fellowship - Wellcome Trust
German Centre for Cardiovascular Research (DZHK)
Cancer Research UK
UKRI
Nuffield Department of Population Health (NDPH)
MRC
Swedish Research Council (Vetenskapsradet)
Swedish Heart Lung Foundation (Hjart-Lungfonden)
British Heart Foundation (BHF)
National Institutes of Health (NIH)
MRC Human Genetics Unit program (QTL in Health and Disease)
Qatar National Research Fund
ReumaNL
Netherlands Organization for Scientific Research NWO-VICI
NWO Gravitation grant ExposomeNL
NWO KIC
ZonMW ME/CFS
EU
Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS), China
European Union (ERC)
DZHK (German Centre for Cardiovascular Research) site Berlin
Biomedical Research Program at WCMQ - Qatar Foundation
Knut and Alice Wallenberg Foundation
European Academy of Allergy and Clinical Immunology (EAACI)
European Respiratory Society (ERS)
British Heart Foundation
National Institute for Health and Care Research Oxford Biomedical Research Centre
British Heart Foundation Oxford Centre of Research Excellence
Nuffield Department of Population Health, University of Oxford, UK
Swedish Heart Lung Foundation
Brain Foundation
RCUK Innovation Fellowship from the National Productivity Investment Fund
Olle Engkvist Foundation for proteomics analyses
National Key Research and Development Program
National Natural Science Foundation of China (NSFC)